Today, health problems associated with obesity are some of the most daunting in the United States. Gut microbiota, microorganisms that live in the digestive tract, are one of the triggers of metabolic syndrome (insulin resistance, hypertension, elevated cholesterol, increased risk for blood clotting, and obesity). While we are born germ-free from a sterile womb, our intestinal tract is rapidly colonized by microbes like bacteria, fungi, and even protozoan parasites, which collectively become our microbiome. From birth until we reach adulthood, our intestine carries about ten times as many microorganisms as all the cells in the rest of our body.
The adult human host produces roughly 6-10 grams of secretory immunoglobulin A (SIgA) into the gut lumen daily, where it binds 30-50% of the 1013-1014 microbes that inhabit the intestine. As a consequence, a significant portion of microbial cells in the lumen is coated with IgA, a smaller fraction with IgG and IgM. The majority of this IgA is thought to be relatively unselective as it binds antigens that are widely shared amongst gut bacteria, including bacterial flagellum and lipopolysaccharide (LPS).
The gut microbiota can trigger metabolic and inflammatory disease. Transplantation of gut microbiota from affected mice and humans transfers excess adiposity, colitis, and metabolic syndrome to naïve germ-free hosts (Feng et al., J. Exp. Med. 207:1321 (2010); Turnbaugh et al., Nature 444:1027 (2006) and Vijay-Kumar et al., Science 328:228 (2010)). Two main mechanisms have been described to explain how microbiota can influence host metabolism: bacterial community composition can affect the efficiency of energy extraction from the diet, liberating excess energy for the host (Turnbaugh et al., Nature 444:1027 (2006)), and alternatively, microbiota can trigger metabolic inflammation leading to reduced insulin sensitivity (Vijay-Kumar et al., Science 328:228 (2010)). It has been shown that the microbiota of mice deficient in Toll-like receptor (TLR) 5 induce metabolic inflammation when transferred to wildtype (WT) germ-free recipients, and that this inflammatory microbiome is less temporally stable, and more enriched in Proteobacteria, compared to WT microbiota (Vijay-Kumar et al., Science 328:228 (2010)). However, the elements of the microbiota that raise its inflammatory potential remain unclear.